Summary This proposal requests R13 support for a longstanding, well-attended, and well-received Gordon Research Conference (GRC) on Excitatory Synapses and Brain Function. The synapse is central to our understanding of circuit function and behavior. In the central nervous system, excitatory synapses represent the primary means of information processing by local circuits and communication between brain regions. Synapses serve as the site of action for many commonly prescribed medications and their disruption contributes to many neurological and psychiatric disorders. These include schizophrenia, autism, depression, substance abuse and addiction, Parkinson's disease, Alzheimer's disease, traumatic brain injury, stroke and epilepsy. In some cases, synaptic dysfunction is causal in disease, whereas in other cases it represents the downstream sequelae of one or more underlying molecular defects. In either case, a fundamental understanding of the formation, structure, molecular organization, signaling function, and plasticity of synapses is essential to progress in lessening the burden of human neurological disease and for predicting and improving mental health. This conference is unique in its focus on the excitatory synapse, and in its multidisciplinary group of participants including structural biologists, molecular and developmental biologists, cell biologists, biochemists, cell/molecular imagers, biophysicists and neurophysiologists. The conference is intended to relate fundamental insights in excitatory synaptic function to the impairments in synaptic function that occur in disease, as well as the maladaptive plasticity that occurs in substance abuse. The goal of the conference is to identify and highlight fundamental new insights into synaptic function, neural circuit dynamics and dysfunction from a thematic approach. The program has been designed to also highlight cutting edge approaches and to stimulate new concepts, methods and technologies within a sound biological framework of fundamental neuroscience. The conference will bring together expert scientists worldwide in an environment that is conducive to discussion and exchange of ideas. The exchange of ideas at this conference has been a driving force for the field. We expect the 2017 GRC on Excitatory Synapses and Brain Function will shape future scientific directions, and provide critical support for the mission of multiple institutes at NIH including NINDS, NIMH, NIDA and NIA.